An effective oral male antifertility agent, which is both non-toxic and reversible, is not currently available. Gossypol, the most promising non-steroidal male antifertility lead, has an unacceptably narrow therapeutic ratio. We propose that the therapeutic ratio may be improved by alteration of the pharmaco-kinetics and bioavailability through water-solubilization. Accordingly, several carefully chosen water-soluble derivatives of gossypol will be prepared. These compounds will then be tested for both in vitro spermicidal activity and in vivo antifertility activity. The in vivo tests will be evaluated both in terms of efficacy and toxicity. The identification of a compound with the same efficacy as gossypol but without the toxic effects would provide the basis for further study leading to the eventual development of a safe and effective male antifertility agent.